Naslov
Genetic variants in RBFOX3 are associated with sleep latency

Autori
Amin, N. ; ... ; Kolčić, Ivana ; ... ; Zgaga, Lina ; ... ; Đogaš, Zoran ; ... ; Borovečki, Fran ; ... ; Polašek, Ozren ; ... ; Rudan, Igor ; ... ; van Duijn, C.M.

Izvornik
European journal of human genetics (1018-4813) 24 (2016), 10; 1488-1495

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
sleep latency, gene

Sažetak
Time to fall asleep (sleep latency) is a major determinant of sleep quality. Chronic, long sleep latency is a major characteristic of sleep-onset insomnia and/or delayed sleep phase syndrome. In this study we aimed to discover common polymorphisms that contribute to the genetics of sleep latency. We performed a meta- analysis of genome-wide association studies (GWAS) including 2 572 737 single nucleotide polymorphisms (SNPs) established in seven European cohorts including 4242 individuals. We found a cluster of three highly correlated variants (rs9900428, rs9907432 and rs7211029) in the RNA-binding protein fox-1 homolog 3 gene (RBFOX3) associated with sleep latency (P- values=5.77 × 10(-08), 6.59 × 10(-)(08) and 9.17 × 10(-)(08)). These SNPs were replicated in up to 12 independent populations including 30 377 individuals (P-values=1.5 × 10(-)(02), 7.0 × 10(-)(03) and 2.5 × 10(-)(03) ; combined meta- analysis P-values=5.5 × 10(-07), 5.4 × 10(-07) and 1.0 × 10(-07)). A functional prediction of RBFOX3 based on co-expression with other genes shows that this gene is predominantly expressed in brain (P-value=1.4 × 10(-316)) and the central nervous system (P-value=7.5 × 10(-) (321)). The predicted function of RBFOX3 based on co-expression analysis with other genes shows that this gene is significantly involved in the release cycle of neurotransmitters including gamma-aminobutyric acid and various monoamines (P-values<2.9 × 10(-11)) that are crucial in triggering the onset of sleep. To conclude, in this first large-scale GWAS of sleep latency we report a novel association of variants in RBFOX3 gene. Further, a functional prediction of RBFOX3 supports the involvement of RBFOX3 with sleep latency.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti, Javno zdravstvo i zdravstvena zaštita

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